Weitere ähnliche Inhalte Kürzlich hochgeladen (20) KG-135 Document Provides Overview of Ginseng Compounds2. CONTENTS
13
21
KG-135
& 15 Agape Medicine
2011
All rights reserved. No part of this publication may be reproduced, stored in a retrieval
system, or transmitted, in any form or by any means, electronic, mechanical, photocopying,
recording, or otherwise, without the prior written permission of the publisher. 17
Printed in Taiwan.
19
KG-135 &
2011.05
192 21X15
ISBN 978–986–6552–86–1
1. 2. 3.
414.34 100008505
主編 詹治東
監修 詹瑩璽
審訂 朴萬基、朴政一
出版發行 唐山出版社|Tonsan Publications Inc. 23
10647 臺北市大安區羅斯福路三段333巷9號B1
tel 02–2363–3072
fax 02–2363–9735
tonsan@ms37.hinet.net
http://blog.yam.com/tsbooks/
出版日期 2011.05
2 定價 NT $ 250 3
3. Part 1 Part 2
27 55 11
31 57 7
7
34
39 79 4
DNA
47
4 5
4. Part 3 116
KG-135
85 KG-135
KG-135
89 KG-135
KG-135
KG-135
124
100 KG-135
Part 4
113
115
6 7
5. Part 5
Q&A 176
177
169
170
178
171
179
172
180
173 181
182
174
183
175
8 9
6. 184
185
186
187
188
189
190
10 11
8. Agape Medicine
2008 1 1
40-70
Agape Medicine
4% dark material
23% dark energy
73%
KG-135
&
Agape
14 15
10. 1995 9
11
50
40-70
KG-135
10-30
70 10
&
18 19
11. 20
2000 12
10
2005
2010
KG-135
&
20 21
13. 1. 2. 3.
4.
Part 1
KG-135
&
24 25
15. . D. Dr. Ernst. D. Prinzenberg
Ginsenosides
Ra1 Ra2 Ra3 Rb1 Rb2 Rb3 Rc
Panaxdiolegroup
Rd Rg3 Rh2 Rs1 Rs2
Ginsenosides
Panaxtriolegroup Re Rf Rg1 Rg2 Rh1 Rh 3
Ginsenosides Ro
O leanolicacid
Phenoles Maltol
B-12,folic acid, nicotine acid, pantothenic
acid, biotin, nicthlamide
Aspartic acid, blycine, alanine, praline,
valine, isoleucine, tyrosine, phenylalanine,
fatty amino acids, arginine
20
200
0.05%
KG-135
&
28 29
16. /
/ panax panacea
KG-135
&
30 31
17. 1
2
6000 300
3
4
5
6
7
8
7
1
2
3
4
5
6
KG-135
7
&
32 33
18. 6
10
36
38
KG-135
&
34 35
19. + +++
+ +++
+ ++
+ ++
+ +++
+ ++
+ ++
+ +++
+ ++
KG-135
3 4 5 6
1.83% 2.09% 2.32% 3.43%
1.59% 1.95% 2.30% 2.79%
&
36 37
20. * M.Kiura
* W.Petkov
* J.Ishigami
* DNA M.Yamamoto
* H.G. Chai
* I.Murata
1960
* S.Odashima
* H.Oura
* M.Yamamoto
* C.N. Joo
* B.H. Han
I.I. Brekhman 1969
* S.J.Fulder
* E.V.Avakian
* E.Bombardelli
* D.J. Lee
* I.Murata
* M.Yonezawa
N.Saito
*
Subhuti 6%
*
Dharemanda
*
C.N. Joo
* J.B. Kim
KG-135
* H.Matsuda
* T.Saito
* V.D.Petkov
* O.Tanaka
&
* S.K.F.Chong
* Masao Haneda
38 Shojvo Ikematsu 39
21. 40
R 3O
OH
R 1O
R2
Ginsenoside R1 R2 R3
Rb1 Glc-Glc- H Glc-Glc-
Rb2 Glc-Glc- H Ara(p)-Glc-
Rc Glc-Glc- H Ara(f)-Glc-
Rd Glc-Glc- H Glc-
Rg3 Glc-Glc- H H
100 Rs3 Ac-Glc-Glc- H H
Re H Rha-Glc-O- H
100 100 Rg1 H Glc-O- Glc-
Rg2 H Rha-Glc-O- H
Rf H Glc-Glc-O- H
Rh1 H Glc-O- H
KG-135
&
40 41
22. Rg3 Ginsana
10 Rg3
1
Ginsana
G115
Pharmaton
Ginsana
Ginsana
1
KG-135
&
42 43
23. Rh2 Rg3 Rk1
Rk1
Drug Rk1 Taxol
Cell line (μg/ml) (μg/ml)
SK-OV-3(卵巢癌細胞) 3.9 ± 0.80 2.3 ± 0.37
NIH:OVCAR-3 (卵巢癌細胞) 18.9 ± 0.21 10.5 ± 3.58
DU-145(攝護腺癌細胞) 21.0 ± 4.24 12.5 ± 2.12
PC-3 (攝護腺癌細胞) 19.0 ± 2.83 4.0 ± 2.80
MCF-7(乳癌細胞) 24.0 ± 0.00 25.5 ± 0.71
HL-60(骨髓性白血病) 5.2 ± 0.08 2.7 ± 0.46
500 1
KG-135
37
1 1
&
44 45
24. Saponin 37 22 14 15
7.47% 3.16% 2.09% 2.25%
Rb1
Rb1
Rb1 Rc
Rb1
Rb1
Rb
Rg1 Rb1 Re DNA RNA
Rh2 Rh3 Rg3
Rg2 Rh1 Rg3 1995
Rg1 Re Rd
Rg1 11
Rb1 Rb2 Rc Re
KG-135
Rg1
Rb1
&
46 5% 100 47
25. 11
500
70 10
40-70 10-30
p.50 p.51
5
100 5
995
KG-135
95%
&
48 49
26. 1987
1987-1989 NIH
Northwestern University
1977 University of Wisconsin-Madison
1987 University of Pittsburgh 1986-1990 Wurzburg
KG-135
1987 1993
&
( )
50 51
1987 2001
27. 1
Anti-oxidant activity SG
0.8
100 WG
0.6
survival
80 0.4
0.2
2
% Inhibition
60
0 Part
0 200 400 600 800 1000
40 Co n c .(mg /mL)
20
0
0 0.1 0.2 0.3 0.4 0.5 0.6 0.7
Concentration (mg/mL)
1
Anti-cancer activity SG
0.8
1 WG
0.6
SG
survival
0.8 0.4
0.2
WG
0.6
survival
0
0 200 400 600 800 1000
0.4 Co n c .(mg /mL)
KG-135
0.2
&
0
0 200 400 600 800 1000
Co n c .(mg /mL)
52 53
29. 7
Major Constitunets
Ginsenoside Rk1 Rg3 Rg5
Unique Constituents
Ginsenoside Rk2 Rk3 Rg1
Ginsenoside Rs4 Rs5 Rs6 Rs7
Ginsenoside Rh2
11
Rh2
Rg3
Rg1
DNA RNA
Rg5,Rk1
Rs3,Rs4
Rg3,Rg5
Rk1
KG-135
&
56 57
31. Chemoprevention Activity
100
80
60
% Inhibition
40 SG
RG
WG
20
0
0 2 4 6 8
Concentration mg ginseng/mL
J. Nat. Prod. 63, 1702 2000
Cancer Letters 150, 41 2000
KG-135
&
60 61
32. 致癌物
1~2 days 1-
排出體外
>10 years 2-
1-解毒癌變物質
促進
>1 year
癌化前細胞
4
4-
1.
2.
3.
腫瘤細胞 3-
KG-135
4.
&
Apoptosis
62 63
33. Anticancer Activity
1
0.8
60~120
0.6 SG
Survival
RG
0.4
WG
0.2
0
0 200 400 600 800 1000
Concentration mg ginseng/mL Rg3 Rg5 Rk1 Rs4 Rh2
Apoptosis Rg3 Rg5 Rk1
Cancer Letters 150, 41 2000
Anticancer Research 19, 487 1999
Anticancer Research 17, 1067 1997
apoptosis
KG-135
&
64 65
34. Control DMBA + TPA
300mg/kg
22
0 1 2 3 22 weeks
DMBA TPA TPA TPA TPA TPA TPA TPA TPA
Initiation Promotion
KG-135
DMBA + TPA
HL60
&
-
- 100 mg/kg
- 300 mg/kg
66 67
35. Vascular, relaxation activity 90.0
SG
80.0
RG 70.0
WG 60.0
50.0
40.0
30.0
20.0
10.0
0.0
5.5 5.0 4.5 4.0 3.5 3.0 2.5
conc. (-log C)
J. Nat. Prod. 63,1702 2000
Eur. J. Pharmacology 367, 41 1999 51 1999
Advances in Ginseng Res. 182 1998
KG-135
&
68 69
36. Rg3 Rg5 Rk1
Kidney protection activity
1.5
150
120
Swimming time min
90
60
KG-135
30
0
Control +Ginseng
&
Swimming test
70 71
37. 100 mg/kg/day, ,
1300 1240
1200
1100 1040
Tumor size
Tumor size
1000
890
900
Cisplatin
800
690
Cisplatin BUN 700
Creatinine 600
500
+
100 mg/kg/day, ,
90
85
80
Blood cholesterol level mg/dl
1000
Survival day
75
800 70
65
600 60
KG-135
55
400
50
200 45
&
40
0
Control +Ginseng
+
72 73
38. Anti-platelet Aggregation
4
3.5
Rg3
3
2.5
2
1.5
1
0.5
0
+ control cisplatin cisplatin
+
선삼 Rg3
Korean Patent 1998-033461 1998-08-18
Biological Pharmaceutical Bull., 21, 79 1998
Korean J. Ginsengscience, 21, 132 1997
KG-135
&
Rg3
74 75
39. Brain Cell Protection Activity
Water maze experiment
20 mg/kg, p.o. 7th day
40
35
30
25
20
15
10
5
0
Control SG
Passive avoidance test
5 mg/kg, , 7th day
SOD
250
200
150
KG-135
100
50
&
0
Control SG Rg3
76 77
40. 100
4
70 50 20 10
Acetylcholine
9
8
7
Concentration ng/mg
6
5
4
3
2
1
0
Control 鉆葚
KG-135
After oral administration for 7 days, 50 mg/kg.
Acetylcholine concentration in Hippocampus
&
78 79
41. DNA
99.5%
Saponin
soap
DNA
92%
30 50
70
KG-135
&
80 81
43. KG-135
KG-135
KG-135
KG135 Rk1 Rg3 Rg5
HPLC data
Rg1,Re Rb1 Rb2
Rd
White
Ginsneg
Rc
Red
Ginseng
Rg3 Rk1 Rg5
S.G.
KG-135
84 85
44. KG-135
1.4
1.2
KG-135
1 Rg3
Rg3
Rg5
Rg5
survival
Rk1 0.8
Rk1
0.6
MTT
0.4
1.2000
0.2
1.0000
0.8000
0
0 20 40 60 80 100
0.6000
Concentration (mg/mL)
(mg/mL)
Survival
0.4000
0.2000
Rs3 Rs4, Rs5
0.0000
0.00 2.75 5.50 8.25 11.00 13.75 16.50 19.25 22.00 24.75 27.50 30.25 33.00 35.75 38.50 41.25 44.00 46.75 49.50
Time min.
HPLC separation – Fraction collection – MTT assay
KG-135
&
KG-135
86 KG-135 87
45. KG-135
CH2 CH CH (C C)2 (X) (CH2)6CH3
R Polyacetylene
O
OH HO
OH KG-135
O
Maltol
Ginsenoside Rg3
Glc Glc O
Ginsenoside Rg5
KG-135
OH
Ginsenoside Rk1
&
KG-135
Glc Glc O
88 89
46. PC-3
Morphology of PC-3 SP cells
200 X 400 X
KG-135 PC-3
PC- 3
KG-135 PC-3
Effect of KG135 on cell viability of PC-3 prostate cells
100
24 h
Cell viability (% of control)
48 h
80 72 h
60
40
KG-135
20
0
&
0 2 5 10 20 40 50 60 80 100
KG-135
Concentration (mg/ml)
90 91
47. KG-135 PC- 3 KG135 inhibited PC-3 cell migration
Effects of KG135 on side population of PC-3 prostate cells
Control
5 g/ml KG135
1.1% 0.4%
KG135
PC – 3
7.5 g/ml KG135
+25 mM Verapamil
0.2%
10 g/ml KG135
Side population
1.1 % 5
+ 25 mM Reserpine
mg/ml KG-135 0%
KG-135
0%
KG-135
&
KG-135
92 93
48. KG-135
Apoptosis
KG-135 Apoptosis
Autophagy
KG-135
&
KG-135
94 http://www.nature.com/onc/journal/v23/n16/images/1207521f4.jpg 95
49. Apoptosis inducing effect of KG-135 KG-135
Hydroxychloroquine A549
SKOV-3
Western blot ananysis of A549 human lung cancer cells
treated with KG135 for 72 h
4.88% 27.55%
6.44%
KG 135 g/ml
Control 50 75 100
Control
Control 10 m
10 g/ml
g/ml 30 30mg/ml
g/ml
FAK
KG135 A549
p-FAK
Akt
NIH:OVCAR3
LC3-II
LC3-I LC3-I KG-135
LC3-II
10.03% 29.04
14.18%
% GAPDH
KG-135
Control 10 g/ml 20 g/ml
&
KG-135
96 97
50. Western blot ananysis of A549 human lung cancer cells 3
treated with KG135 for 72 h A549 lung cancer cells 3 days of treatment A549
KG135 50 g/ml
KG135
Hydroxychloroquine 25 M
A549
FAK
p-FAK
Akt
Control KG135 75 g/ml
LC3-II
LC3-I LC3-I
KG-135
LC3-II
GAPDH
H-CQ 25 KG135 75 g/ml+H-CQ 25 M
KG-135
&
KG-135
KG135
98 A549 KG-135 99
51. KG-135 DBTRG 05MG glioblastoma cells 72 h treatment
H-CQ
KG-135 Hydroxychloroquine
DBTRG05MG
KG-135 Hydroxychloroquine KG135
DBTRG05MG DBTRG 05MG
DBTRG 05MG glioblastoma cells 72 h treatment
H-CQ
KG-135
&
KG135
KG-135
DBTRG 05MG
100 KG-135 101
52. KG-135 matformin KG-135
A549
Chemoprevention activity
KG-135 matformin
A549
01/24
DMBA + TPA
DMBA + TPA+
100 mg
KG135 metformin
A549
KG-135
DMBA + TPA+
500 mg
&
KG-135
102 103
53. KG-135 Standardized SG extract inhibits TPA- Effects of KG-135 on phorbol ester-induced cox-2
induced COX-2 expression in human breast epithelial expression and ERK activation in mouse skin
MCF-10A cells.
+ KG-135 mg/kg
0 100 500
KG-135
Control
+ TPA
TPA
COX-2 COX-2
Actin
Actin
pERK
KG-135
TPA
COX-2 ERK
Gapdh
KG-135 inhibits cox-2 expression and ERK activation
KG-135 inhibits TPA-induced cox-2 expression in MCF-10A cells
KG-135
COX-2 + TPA
COX-2 + TPA KG-135
&
KG-135
KG-135
104 105
54. Effect of KG-135 on TPA-Induced Subsequent
Degradation of Icy-a, and on NF-kB DNA Binding in
Mouse Skin Treated with TPA
120
+ KG-135 mg/kg
0 100 500
100
Control
+ TPA
% Mice with tumors
Control
IkB-a 80 Control+SG 100mg/kg
60
Control+SG 500mg/kg
IkB-a 40
20
Control_negative
Actin 0
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Weeks
IkB-a
NF-kB TPA +
Co only
KG-135(mg/kg)
l
ro
p.
e
A
ob
nt
m
TP
0
KG-135
0
Co
50
Pr
10
KG-135
NF-kB
&
KG-135
106 107
55. KG-135 SG-unique constituents inhibits COX-2 expression KG-135 inhibits BrDU and PCNA in vivo
by blocking the activation of JNK and AP-1 in phorbol ester-
DMBA + TPA
stimulated human breast epithelial cells.
KG-135 KG-135
Control Acetone DMBA + TPA 100mg/kg 500mg/kg
KG-135
TPA
JNK
JNK
BrDU
KG-135
KG-135 JNK
KG-135
KG-135
on obe
KG-135 - - +
pr ld
e
pr
ly
ob
TPA - -
co
+ + +
AP-1 PCNA
激活蛋
白
KG-135
&
KG-135
108 109
56. 100
DMBA-TPA
80 + 0.1% SG
% Tumor bearing mice
60
+ 0.5% SG
Part 4
40
20
0
0 2 4 6 8 10 12 14 16 18 20 22
Week
Cancer Letters, 150, 41 2000
Topical application of SG 10 min prior to TPA application
KG-135
&
110 111
58. 1.
2.
3.
2005
KG-135
&
114 115
59. 100mg 200mg
5~7
250mg
250mg
500 mg
1000mg
15
KG-135
&
116 117
61. 11.
12.
1.
13.
14.
2.
15.
3.
16.
17.
4.
18.
19.
5.
20.
6.
21.
7.
22.
8.
23.
9.
KG-135
45.
10:
25.
&
26.
120 121
62. 27. 42.
28. 43.
29.
44.
30.
45. /
31.
32.
33.
34.
35.
36.
37.
38.
KG-135
39.
40.
&
41.
122 123
63. 54
60
55
76
KG-135
1000
mg
&
124 125
64. 59
15
1000 mg
25 1500 mg
1500 mg
7 3
2.6
10 3 25 3
29
Mrs.Lube 56
68
Mrs.Lube Mr.Lube
1000 mg 1000
mg Mr.Lube
KG-135
50
&
126 127
65. 43 68
20 PSA 78.4
250 mg 0~4
15 1000 mg PSA 25
2000 mg
4
40
GOT GPT
50
1500 mg
3-6
2000 50
KG-135
mg
4 2
&
128 129
66. 78
700
4.3 1000 mg
700 1500 1500
1000 mg 3500 7000
4.3
3.4
48
50
50 20
30
32
KG-135
&
130 131
67. 50
7
KG-135
12-15
&
132 133
69. 55
55
4~5 57
5~6
45
KG-135
&
136 137
70. 54
Rg3 Rg5 Rk1
KG-135
&
138 139
71. 87
58
3
4
BUN
3 2 80
4
2
85
KG-135
&
140 141
72. 45
GOT/GPT 140
GOT GPT 40
57
GOT GPT 400
GOT GP
45
KG-135
&
142 143
73. 48
60
GOT GPT 400
GOT GPT 400
100 42 37 29
60
2 3
100mg
96 11
KG-135
B
&
B
144 145
74. GOT GPT
GOT GPT
1 mg
1.
2.
KG-135
3.
4.
5.
&
146 147
75. 33
25 23
8
55
30
KG-135
&
148 149
76. 58
55
KG-135
4~5
&
5~6
150 151
77. 55
60
30
60 B 150
150
54 150 100
55
10
360
330 280 200 168
200
KG-135
&
152 153
78. 60
15%~20%
72
60
KG-135
&
154 155
79. 55
60
1-2
KG-135
&
156 157
80. 55
10
360
36 72
330 280 200 168
200
55
11
KG-135
30
&
158 159
81. 60
B B
96 11
B
2
B
55
160
170
120-140
KG-135
&
160 161
82. 40
26
1
30
5 6
KG-135
35
45
&
162 163
85. Q
A B.C.
180
113
21 18.6%
Q
A
Q&A
168 169
86. Q
Eurekatert A
Guardian 1.
2.
Q
A 3.
4.
Q
Q
A A
95%
KG-135
&
Q&A
170 171
87. Q
A
Q
Q A
A 1.
1 2.
2 3.
3 4.
1 2
3
Q
A
KG-135
Q
A
&
Q&A
172 173
88. Q
Q
A A
Q Q
A A
Q
A
KG-135
5 /1
60
300 Q
&
55 A
Q&A
174 27 175
89. Q
A
Q Q
A
A
50%
20% 30
Q
A
KG-135
&
Q&A
176 177
90. Q Q
A A
30 30
1
1-7
1 1
1
1-7
1 1 1 30
1-7
2 1 1
Q
1-7
2 2 1
A
1-7
2 2 2
500C.C.
1-7
Q
500C.C.
700mg 480mg 500mg
Q
500mg 254mg 100mg
KG-135
11 11 11 A
&
Q&A
178 179
91. Q
Q A
A
5-20
KG-135
Q
A
&
1 2
Q&A
180 181
92. Q
A
Q
A
1. Q
2. A
3.
Q
A
BUN
Creatinine
KG-135
Q
A
Q
&
Q&A
182 A 183
93. Q
A
Q
A
Q
A Q
A
Q
KG-135
A
&
Q&A
184 185
94. Q
A
Q
Q
A A
Q
KG-135
Q
A A Ginsenoside Rg3
&
Q&A
186 187
95. Q
A
Q
A
Q
A
Q
Q
A A
1.
KG-135
2.
3.
&
Q&A
188 189
96. 4.
Q
A
1.
2. 15
15
3.
KG-135
4.
&
Q&A
190 191